Hydroxylation of aromatic acids

ABSTRACT

The nuclear hydroxylation of a nuclearly substituted aromatic acid is accomplished by treating the acid with hydrogen peroxide in the presence of substantially anhydrous hydrogen fluoride at a temperature in the range of from about -10* to about 100* C.

United States Patent [451 July 18, 1972 Vesely et al.

[54] HYDROXYLATION OF AROMATIC ACIDS a [72] Inventors: Jerome A.'Vesely, Park Ridge; Louis Schmerllng, Riverside, both of III.

[73] Assignee: Universal Oil Products Company, Des

Plaines, Ill.

[22] Filed: Sept. 29, 1969 [21] Appl. No.: 862,007

[52] US. Cl. ..260/52l R, 260/520, 260/479 R [5 l Int. Cl ..C07c 65/02[58] Field of Search ..260 /52l R, 520

References Cited OTHER PUBLICATIONS Universal Oil Products Co., Chem.Abst. 68 68700n 1968) Primary Examiner-Lorraine A. Weinberger AssistantExaminer.lohn F. Tenapane Attorney-James R. Hoatson, Jr. and Raymond H.Nelson [57] ABSTRACT 6 Claims, No Drawings HYDROXYLATION OF AROMATICACIDS This invention relates to a process for the hydroxylation ofaromatic acids. More particularly, the invention is concerned with aprocess for the nuclear hydroxylation of a substituted aromatic acidwhereby one or more hydroxyl groups are introduced on the aromaticnucleus of the acid.

l-lydroxylated aromatic acids are finding a wide variety of uses in thechemical field. For example, a-resorcylic acid which is3,5-dihydroxybenzoic acid is used as an intermediate for dyes, forpharmaceuticals and for light stabilizers and resins; B-resorcylic acidwhich is 2,4-dihydroxybenzoic acid is also used as a dyestuff, as anintermediate in the preparation of pharmaceuticals or in the synthesisof fine organic chemicals. A third isomer of the dihydroxybenzoic acidwhich is gentisic acid (2,5-dihydroxybenzoic acid) is used in medicineas sodium gentisate. Another hydroxylated aromatic acid is gallic acid(3,4,5-trihydroxybenzoic acid) which is used for a variety of purposesincluding its use in photography, writing inks, dyeing, in themanufacture of pyrogallol which itself has many uses, as a tanning agentand in the manufacture of tannins, in paper manufacture; in synthesis ofpharmaceuticals, in process engraving and lithography, etc.

It is therefore an object of this invention to provide a process forpreparing hydroxylated aromatic acids. A further object of thisinvention is to provide a process for introducing hydroxyl substituentson the nucleus of a substituted aromatic acid to provide useful chemicalcompounds.

In one aspect an embodiment of this invention resides in a process fornuclear hydroxylation of an aromatic acid which possesses the genericformula:

in which R is independently selected from the group consisting ofhydrogen, alkyl, cycloalkyl, aryl, alkaryl, aralkyl, hydroxy, alkoxy andacyloxy radicals, Ar is an aromatic hydrocarbon nucleus, n is an integerof from 1 to 3 and m is an integer of from O to about 10, at least one Rbeing other than hydrogen when rn is 0, which comprises treating saidaromatic acid with hydrogen peroxide in the presence of hydrogenfluoride at a temperature in therange of from about l to about 100 C.,and recovering the resultant hydroxylated aromatic acid.

A further embodiment of this invention is found in a process for thenuclear hydroxylation of an aromatic acid which comprises treating saidacid with an aqueous solution of hydrogen peroxide containing from about5 percent to about 90 percent of hydrogen peroxide in the presence ofhydrogen fluoride at a temperature in the range of from about l0 toabout 100 C. and at ambient pressure, and recovering the resultanthydroxylated aromatic acid.

A specific embodiment of this invention is found in the process for thenuclear hydroxylation of salicylic acid which comprises treating saidacid with an aqueous solution of hydrogen peroxide containing from about5 percent to about 90 percent hydrogen peroxide in the presence ofhydrogen fluoride at a temperature in the range of from about 0 to about40 C. and at ambient pressure, and recovering the resultantdihydroxybenzoic acids.

Other objects and embodiments will be found in the following furtherdetailed description of the present invention.

As hereinbefore set forth the present invention is concerned with aprocess for introducing hydroxyl substituents on the nucleus of anaromatic acid, said hydroxylation being effected by treating asubstituted aromatic acid with hydrogen peroxide in the presence ofhydrogen fluoride in a manner hereinafter set forth in greater detail.While it is known that certain aromatic compounds can be hydroxylatedutilizing hydrogen peroxide in the presence of hydrogen fluoride, wehave found that it is impossible to hydroxylate benzoic acid in thismanner. However, it has now been discovered that when an aromatic acidcontains an activating substituent of the type hereinafter set forth ingreater detail, the acid is reactive and may be hydroxylated to yieldthe desired hydroxylated aromatic acid derivative. The term aromaticacid as used in the present specification and appended claims will referto these acids which contain an activating substituent.

Aromatic acids which comprise suitable starting materials for theprocess of this invention possess the generic formula:

R,,Ar(CR,),,,COOH

in which R is independently selected from the group consisting ofhydrogen, alkyl, cycloalkyl, aryl, alkaryl, aralkyl, hydroxy, alkoxy andacyloxy radicals, Ar is an aromatic hydrocarbon nucleus, n is an integerof from 1 to 3 and m is an integer of from 0 to about 10, at least one Rbeing other than hydrogen when m is 0. lt is contemplated that compoundsin which R may comprise another carboxy group, a halogen atom or a nitrogroup may also be utilized provided that a second R in the moleculecomprises an alkyl, hydroxy, alkoxy or acyloxy substituent, but notnecessarily with equivalent results. The aromatic hydrocarbon nucleus ofthe formula which is designated Ar may comprise a benzene, naphthalene,anthracene, phenanthrene, chrysene, pyrene or biphenyl nucleus. Somespecific examples of these acids which will undergo nuclearhydroxylation will include o-toluic acid, n-toluic acid, p-toluic acid,o-ethylbenzoic acid, m-ethylbenzoic acid, p-ethylbenzoic acid,o-propylbenzoic acid, m-propylbenzoic acid, p-propylbenzoic acid,o-isopropylbenzoic acid, m-isopropylbenzoic acid, p-isopropylbenzoicacid, o-t-butylbenzoic acid, m-t-butylbenzoic acid, p-t-butylbenzoicacid, 2,4-dimethylbenzoic acid, 2,5-dimethylbenzoic acid, 2,6-dimethylbenzoic acid, 2,4-diethylbenzoic acid, 2,5-diethylbenzoic acid,2,6-diethylbenzoic acid, 2,4-dipropylbenzoic acid, 2,5-dipropylbenzoicacid, 2,6-dipropylbenzoic acid, 2,4- diisopropylbenzoic acid,2,5-diisopropylbenzoic acid, 2.6- diisopropylbenzoic acid,2,4,6-trimethylbenzoic acid, 0- cyclohexylbenzoic acid, mcyclohexylbenzoic acid. pcyclohexylbenzoic acid, o-phenylbenzoic acid,m-phenylbenzoic acid, p-phenylbenzoic acid, o-benzylbenzoic acid.mbenzylbenzoic acid, p-benzylbenzoic acid, o-p-tolylbenzoic acid,m-p-tolylbenzoic acid, p-p-tolylbenzoic acid, salicylic acid,4-methylsalicylic acid, 4-ethylsalicylic acid, 2,4- dihydroxybenzoicacid, o-methoxybenzoic acid, m-methoxybenzoic acid, p-methoxybenzoicacid, o-ethoxybenzoic acid, m-ethoxybenzoic acid, p-ethoxybenzoic acid,phenylacetic acid, p-methylphenylacetic acid, p-ethylphenylacetic acid,0- hydroxy-phenylacetic acid, m-hydroxyphenylacetic acid,phydroxyphenylacetic acid, o-methoxyphenylacetic acid,mmethoxyphenylacetic acid, p-methoxyphenylacetic acid, 0-ethoxyphenylacetic acid, m-ethoxyphenylacetic acid, p-ethoxyphenylaceticacid, 2-phenylpropionic acid, 3-phenylpropionic acid,2-(o-methylphenyl)propionic acid, 2-(mmethylphenyl)propionic acid,2-(p-methylphenyl)propionic acid, 2-(o-hydroxyphenyl)propionic acid,Z-(m-hydroxyphenyl) propionic acid, 2-(p-hydroxyphenyl)propionic acid,3-(omethylphenyl)propionic acid, 3-(m-methylphenyl)propionic acid,3-(p-methylphenyl)propionic acid, 3-(o-hydroxyphenyl)propionic acid,3-(m-hydroxpyhenyl)propionic acid, 3-(phydroxyphenyl)propionic acid,2-phenylbutyric acid, 3-phenylbutyric acid, 4-phenylbutyric acid,2-(o-hydroxyphenyl)butyric acid, 2-(m-hydroxyphenyl)butyric acid,2-(p-hydroxyphenyl)butytic acid, 3-(o-hydroxyphenyl)butyric acid,3-(mhydroxyphenyl)butyric acid, 3-(p-hydroxyphenyl)butyric acid,4-(o-hydroxyphenyl)butyric acid, 4-(m-hydroxyphenyl)butyric acid,4-(p-hydroxyphenyl)butyric acid, 2-, 3-, 4- or S-phenyl-valeric acids,2-, 3-, 4-, 5- or 6-phenylhexanoic acids, etc., l-methyl-Z-naphthoicacid, l-ethyl-2-naphthoic acid, 1- propyl-2-naphthoic acid,l-hydroxy-2-naphthoic acid, l-phenyl-2-naphthoic acid,l-benzyl-Z-naphthoic acid, l-p-tolyl-2- naphthoic acid,3-methyl-2-naphthoic acid, 3-ethyl-2- naphthoic acid,3-propyl-2-naphthoic acid, 3-hydroxy-2- naphthoic acid,3-phenyl-2-naphthoic acid, 3-benzyl-2- naphthoic acid,3-p-tolyl-2-naphthoic acid, the corresponding carboxylic acids ofanthracene, phenanthrene, chrysene, pyrene, etc. It is to be understoodthat the aforementioned aromatic acids containing a reactive substituentare only representative of the class of compounds which may be used, andthat the present invention is not necessarily limited thereto.

The process of this invention is effected by treating an aromatic acidof the type hereinbefore set forth in greater detail with hydrogenperoxide in the presence of a catalyst comprising hydrogen fluoride. Thehydrogen peroxide may be present in an aqueous solution containing from5 up to 90 percent or more hydrogen peroxide. The preferred hydrogenperoxide solution will contain a 30-50 percent or higher concentrationof hydrogen peroxide inasmuch as when utilizing a lesser amount, theaqueous portion of the solution will tend to dilute the catalyst whichis preferably charged to the reaction zone in anhydrous form. When theconcentration of the hydrogen fluoride catalyst falls below a figure ofabout 60 to 70 percent, the reaction will slow down and eventuallycease; therefore, it is necessary to maintain the concentration ofhydrogen fluoride in an amount greater than 60 percent and preferablygreater than 80 percent and thus necessitate the use of a relativelyconcentrated hydrogen peroxide solution. It is also contemplated, if sodesired, that an additional compound such as boron trifluoride or aferrous fluoborate having the formula FeF -BF may be utilized as apromoter to increase the catalytic acidity and thereby permit thereaction to proceed in such a manner as to provide increased yields ofthe desired product. In addition, the reaction is effected underhydroxylation conditions which will include temperatures ranging fromabout l0 up to about 100 C. or more and preferably at a temperature inthe range of from about 0 to about 40 C. The reaction pressure which isutilized will preferably comprise ambient pressure, although somewhathigher pressure may be used, the pressure being that which is necessaryto maintain a substantial portion of the reactants and the catalyst inthe liquid phase.

The obtention of either a monohydroxylated aromatic acid orpolyhydroxylated aromatic acid can be varied according to the amount ofaromatic acid which is treated with the hydrogen peroxide. For example,if a monohydroxylated aromatic acid is desired, an excess of thestarting aromatic acid will be used. Conversely, if a polyhydroxylatedaromatic acid comprises the desired product, the relative amount ofhydrogen peroxide which is used will be increased. Generally speaking,the aromatic acid will be present in a mole ratio in the range of fromabout 3:] to about moles of aromatic acid per mole of hydrogen peroxide,although greater or lesser amounts of aromatic acids may also be used.

The process of the present invention may be effected in either a batchor continuous type operation. For example, when a batch type operationis used, a quantity of aromatic acid is placed in an appropriateapparatus such as, for example, a stirred autoclave, along with thehydrogen fluoride. The hydrogen peroxide is added thereto and thereaction allowed to proceed for a predetermined residence time under thehydroxylation conditions hereinbefore set forth in greater detail. Theresidence time may vary from about 0.5 hour up to about 5 hours or morein duration. Upon completion of the desired residence time, the catalystis purged from the reactor utilizing a stream of inert gas such asnitrogen and the reaction product thereafter recovered. Following this,the reaction product is subjected to conventional means for recovery,said means including washing the product with an inert organic solvent,neutralization of any hydrogen fluoride which may still be present,flashing off the solvent and subjecting the reaction product tofractional distillation or recrystallization to recover the desiredcompounds.

it is also contemplated that the process of this invention may beeffected in a continuous manner of operation. When such a process isused, the aromatic acid is continuously charged to a reaction zone whichis maintained at the proper operating conditions of temperature andpressure. In addition, the hydrogen peroxide in the form of an aqueoussolution containing from 5 percent up to about 90 percent or morehydrogen peroxide is continuously charged to the reaction zone. Thereaction is allowed to proceed in the presence of a hydrogen fluoridecatalyst present in the reactor or continuously charged for apredetermined time of from about 0.0] hour to about 2 hours, followingwhich the reactor effluent is continuously withdrawn. The hydrogenperoxide and the hydrogen fluoride may be premixed and the resultingsolution fed continuously to the reactor. The reaction product isseparated from the catalyst and the former is subjected to treatmentsimilar to that hereinbefore set forth to recover the desiredhydroxylated aromatic acid.

Examples of hydroxylated aromatic acids which may be prepared accordingto the process of this invention include 5- hydroxy-o-toluic acid,3,5-dihydroxy-o-toluic acid, S-hydroxym-toluic acid, S-hydroxy-p-toluicacid, 3,5-dihydroxy-p-toluic acid, 5-hydroxy-2-ethylbenzoic acid,5-hydroxy-3-ethylbenzoic acid, 3-hydroxy-4-ethylbenzoic acid,3,5-dihydroxy-4-ethylbenzoic acid, S-hydroxy-Z-propylbenzoic acid,5-hydroxy-3- propyl-benzoic acid, 3-hydroxy-4-propylbenzoic acid, 3,5-dihydroxy-4-propylbenzoic acid, 5-hydroxy-2-isopropylbenzoic acid,5-hydroxy-3-isopropybenzoic acid. 3-hydroxy-4- isopropylbenzoic acid,3,5-dihydroxy-4isopropylbenzoic acid. 5-hydroxy-o-t-butylbenzoic acid,S-hydroxy-3-t-butylbenz0ic acid 3-hydroxy-4-t-butylbenzoic acid,3,5-dihydroxy-4-t-butylbenzoic acid, 5-hydroxy-2,4-dimethylbenzoic acid.3- hydroxy-2,S-dimethylbenzoic acid, 5-hydroxy-2,6-dimethylbenzoic acid,S-hydroxy-2,4,6-trimethylbenzoic acid, 3.5-dihydroxy-2,4,6-trimethylbenzoic acid, 5-hydroxy2- cyclohexylbenzoicacid, 5-hydroxy-2-phenylbenzoic acid, 3,5- dihydroxy-Lphenylbenzoicacid, 2,3-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid,2,5-dihydroxybenzoic acid, 3,4,5- trihydroxybenzoic acid,2,3-dihydroxy-4-methylbenzoic acid, 2,5dihydroxy-4-methylbenzoic acid,2,3-dihydroxy-4-ethylbenzoic acid, 2,5-dihydroxy-4-ethylbenzoic acid,S-hydroxy- 2-methoxybenzoic acid, 5hydroxy-2-methoxybenzoic acid,3,5-dihydroxy-4-methoxybenzoic acid, 5-hydroxy-2-ethoxybenzoic acid,3-hydroxy-4-ethoxybenzoic acid, 3,5-dihydroxy-4-ethoxybenzoic acid,4-hydroxyphenylacetic acid, 2,4- dihydroxyphenylacetic acid,4-hydroxy-3methylphenylacetic acid, 4-hydroxy-3-ethylphenylacetic acid,3,4-dihydroxyphenylacetic acid, 2,S-dihydroxyphenylacetic acid,5-hydroxy-2- methoxyphenylacetic acid, 4-hydroxy-3-methoxyphenylaceticacid, 2,5-dihydroxy-4-methoxyphenylacetic acid, 2-(4-hydroxyphenyl)propionic acid, 2-(2,4-dihydr0xyphenyl)propionic acid,3-(4-hydroxyphenyl) propionic acid, 3- (2,4-dihydroxyphenyl)propionicacid, 2-(4-hydroxy-3- methylphenyl)propionic acid,3-(2-hydroxyphenyl)propionic acid, 3-(2,5-dihydroxyphenyl)propionicacid, 2-(4-hydroxyphenyl) butyric acid, 3-(4-hydroxyphenyl)butyric acid,4-(4- hydroxyphenyl) butyric acid, 4-hydroxy-lmethyl-2-naphthoic acid,3,4-dihydroxy-l-methyl-Z-naphthoic acid, 1,4- dihydroxy-Z-naphthoicacid, 3,4-dihydroxy-l-naphthoic acid, etc. it is to be understood thatthe aforementioned compounds are only representative of the class ofhydroxylated aromatic acids which may be prepared, and that the processof the present invention as described herein is not necessarily limitedthereto.

The following examples are given to illustrate the process of thepresent invention which, however, are not intended to limit thegenerally broad scope of the present invention in strict accordancetherewith.

EXAMPLE I In this example 136 g. (1.0 mole) of phenylacetic acid wasplaced in a stainless steel turbomixer autoclave. Following this 230 g.(l 1.5 moles) of hydrogen fluoride was charged thereto. Thereafter 10.9g. ofa 30 percent hydrogen peroxide solution was gradually charged tothe reactor during a period of 10 minutes. The mole ratio ofphenylacetic acid to hydrogen peroxide was 10:1. The mixture was stirredfor an additional period of 10 minutes, the temperature during theentire 20 minute contact time being in a range of from 0 to 6 C. bymeans of an ice bath. At the end of the contact time the hydrogenfluoride was swept out of the autoclave with a stream of nitrogen for aperiod of about 2 hours before the autoclave was opened.

The reaction product which comprised 134.7 g. was transferred to abeaker and the reactor parts were washed with benzene, the washingsbeing added to the reaction product. The solution was decanted intoanother beaker thereby separating out a small amount of an aqueous acidphase which contained some benzene-insoluble product. The decantedbenzene solution was treated to remove residual hydrogen fluoride,filtered under suction and distilled to remove benzene and unreactedphenylacetic acid. The benzene-insoluble product was combined with theproduct in the aqueous acid phase and extracted with ether. The extractwas treated to remove residual hydrogen fluoride and subjected todistillation to remove the ether. The bottoms from both product segmentswere combined and subjected to fractional distillation under reducedpressure, there being recovered two crystalline product components whichare found by nuclear magnetic resonance analysis to behydroxyphenylacetic acid isomers.

EXAMPLE [1 In this example 207 g. (1.5 moles) of salicylic acid alongwith 250 cc. of a n-heptane solvent were placed in the glass liner of aone liter stainless steel turbomixer autoclave. Following this 244 g.(12.2 moles) of hydrogen fluoride was charged thereto. Thereafter 51 g.(0.15 mole) of a 30 percent aqueous hydrogen peroxide solution wasgradually charged to the reactor, the peroxide addition beingaccomplished during a period of 16 minutes. The mixture was stirred foran additional period of 14 minutes, the temperature during the entirecontact time being maintained in a range of from about 23 to about 26 C.At the end of the predetermined contact time the hydrogen fluoride wasswept out of the autoclave utilizing a stream of nitrogen for a periodof 2 hours.

After opening the autoclave the reacted product was transferred to abeaker and the reactor parts were washed with benzene, the washingsbeing added to the reaction product. Upon decanting the reaction productinto a second beaker a small amount of an aqueous acid phase whichcontained some benzene-insoluble product was separated out. The decantedbenzene solution was' treated with calcium carbonate to remove residualhydrogen fluoride, filtered under suction and distilled to remove thebenzene and unreacted salicylic acid. The benzene-insoluble productwhich remained in the reactor was combined with the product in theaqueous acid phase and extracted with ether. This extracted product wasalso treated to remove residual hydrogen fluoride and subjected todistillation to remove the ether. The combined product segments weresubjected to fractional distillation under reduced pressure, there beingrecovered a mixture of dihydroxybenzoic acids which were found by meansof infrared analysis and nuclear magnetic resonance to correspond to a35 mole percent yield of 2,3-dihydroxybenzoic, acid, a 35 mole percentyield of 2,5-dihydroxybenzoic acid, and a combined yield ofapproximately 18 mole percent of 2,4-dihydroxybenzoic acid and2,6-dihydroxybenzoic acid.

EXAMPLE [II To a stainless steel turbomixer autoclave was charged 136 g.1.0 mole) of o-toluic acid and 250 cc. of n-pentane which acted as adiluent. The autoclave was immersed in an ice bath so that thetemperature was maintained at a range of from about 0 to about 3 C.during the entire reaction time. Following this 215 g. (10.8 mole) of a30% hydrogen fluoride solution was charged to the reactor and thereafter16.4 g. of a 30 percent hydrogen peroxide solution was slowly added tothe mixture during a period of about 28 minutes. After completion of thehydrogen peroxide addition the mole ratio of o-toluic acid to hydrogenperoxide was 70:1. The mixture was stirred for an additional period of17 minutes while, as hereinbefore set forth, the temperature wasmaintained in a range of from 0 to 3 C. Upon completion of the totalcontact time of 45 minutes, the hydrogen fluoride was purged from thereactor by means of a stream of nitrogen for a period of 2 hours. Thereaction mixture was then poured into a vessel and the autoclave partswashed with benzene. The washings were combined with the reactionproduct which was thereafter treated in a manner similar to that setforth in the above examples. The presence of 5-hydroxy-o-toluic acid wasdetermined by means of infrared and nuclear magnetic resonance analysis.

EXAMPLE lV When hydrogen peroxide was added to a stirred mixture ofbenzoic acid and liquid hydrogen fluoride in a manner similar to thathereinbefore described, while maintaining the temperature of thereaction at about 25 C., no conversion of the benzoic acid tohydroxybenzoic acid or dihydroxybenzoic acid was found.

EXAMPLE V In this experiment 186 g. 1.0 mole) of l-methyl-2-naphthoicacid along with 250 cc. of n-pentane is charged to a turbomixerautoclave, said autoclave being immersed in an ice bath in order tomaintain the temperature'in a range of from about 0 to about 5 C.Following this 215 g. (10.8 mole) of hydrogen fluoride is charged to theautoclave and thereafter 21.8 g. of a 30 percent hydrogen peroxidesolution is slowly added thereto during a period of about 30 minutes.Upon completion of the addition of the hydrogen peroxide the reactionmixture is stirred for an additional 30 minutes to bring the totalcontact time to 60 minutes. At the end of this period the hydrogenperoxide is purged from the autoclave by means of a stream of nitrogen,said purge being accomplished in a period of 2 hours.

The reaction mixture, after opening of the autoclave, is transferred toa vessel, the autoclave is washed with benzene and the benzene washingsare added to the reaction mixture. Upon decanting the solution intoanother vessel, an aqueous acid phase which contains somebenzene-insoluble product will separate out. The decanted benzenesolution is treated with sodium carbonate to remove residual hydrogenfluoride, filtered under suction and subjected to fractionaldistillation to remove the benzene and unreacted l-methyl-Z-naphthoicacid. The benzene-insoluble product which remains in the reactor iscombined with the product in the aqueous acid phase and extracted withether. The extract is again treated to remove residual hydrogen fluorideand thereafter subjected to fractional distillation to remove the ether.The remainder is combined with the other product segment and subjectedto fractional distillation under reduced pressure whereby the desired4-hydroxy-1-methyl-2naphthoic acid is recovered.

EXAMPLE Vl In this example 152 g. 1.0 mole) of 4-methoxybenzoic acidalong with 250 cc. of n-pentane diluent is placed in an autoclave and148 g. (7.4 mole) of hydroxy fluoride is charged thereto. Following this21.8 g. of a 30 percent hydrogen peroxide solution is slowly added tothe autoclave during a period of about 30 minutes. During the hydrogenperoxide addition time and for an additional stirring period of 30minutes, the temperature of the autoclave is maintained in a range offrom about 0 to about 5 by means of an ice bath. upon completion of the60 minute contact time the hydrogen fluoride was flushed from theautoclave by utilizing a stream of nitrogen for a period of 2 hours.

The reaction product is treated in a manner similar to that set forth inthe above examples. After fractional distillation has been completedinfrared analysis will disclose the presence of a mixture ofhydroxymethoxybenzoic acid, chiefly 3-hydroxy-4-methoxybenzoic acid.

We claim as our invention:

l. A process for the nuclear hydroxylation of an aromatic acid whichpossesses the generic formula:

R,,ArCOOH in which R is independently selected from the group consistingof alkyl, hydroxy, alkoxy, acyloxy, cycloalkyl aryl, alkaryl and aralkylradicals, said Ar and aryl are phenyl, n is an integer of from l to 3,which comprises 4. The process as set forth in claim 1 in which saidaromatic treating said aromatic acid with 230% aqueous solution of acidis o-toluic acid and said hydroxylated aromatic acid is hydrogenperoxide in the presence of hydrogen fluoride of at hydroxy-o-toluicacid. least 60 percent concentration at a temperature in the range 5. Thpro ess 38 Set f r h in Claim 1 in which Said aromatic f from bo t oabout 100 C d recovering h 5 acid is salicylic acid and saidhydroxylated aromatic acid is a resultant hydroxylated aromatic acid.dihydr xy acid. I 2. The process as set forth in claim 1 in which saidaromatic The Prom?SS as Set forth Clalm l Whlch 531d aromatic acid is analkypsubstituted aromatic acid acid is 4-methoxybenzoic acid and saidhydroxylated aromatic 3 The process as set forth in claim 1 in whichsaid aromatic a hydroxy4'methoxybenzolc mildacid is ahydroxy-substituted aromatic acid. [0

2. The process as set forth in claim 1 in which said aromatic acid is analkyl-substituted aromaTic acid.
 3. The process as set forth in claim 1in which said aromatic acid is a hydroxy-substituted aromatic acid. 4.The process as set forth in claim 1 in which said aromatic acid iso-toluic acid and said hydroxylated aromatic acid is 5-hydroxy-o-toluicacid.
 5. The process as set forth in claim 1 in which said aromatic acidis salicylic acid and said hydroxylated aromatic acid is adihydroxybenzoic acid.
 6. The process as set forth in claim 1 in whichsaid aromatic acid is 4-methoxybenzoic acid and said hydroxylatedaromatic acid is a hydroxy-4-methoxybenzoic acid.